Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide Turkish cohort study

Kanmaz S., Tekgul H., Kayilioglu H., Atas Y., Kart P. O., Yildiz N., ...Daha Fazla

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, cilt.123, ss.17-25, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 123
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.seizure.2024.09.021
  • Dergi Adı: SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, MEDLINE, Psycinfo
  • Sayfa Sayıları: ss.17-25
  • Anahtar Kelimeler: Early-onset developmental epileptic encephalopathies, Genetic testing, Precision medicine, Stepwise diagnostic model
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Objective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management. Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005-2013) and the current NGS era (2014-2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined. Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs. Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients.